Objective—Arterial calcification is associated with cardiovascular disease as a complication of advanced atherosclerosis. Aged vascular cells manifest some morphological features of a senescent phenotype. Recent studies have demonstrated that mammalian sirtuin 1 (SIRT1), a histone deacetylase, is an exciting target for cardiovascular disease management. Here, we investigated the role of SIRT1 in a calcification model of vascular smooth muscle cells (SMCs). Methods and Results—In adenine-induced renal failure rats with hyperphosphatemia, massive calcification was induced in the aortic media. Senescence-associated β-galactosidase (SAβ-gal) activity, a marker of cellular senescence, in medial SMCs was significantly increased, and its induction was positively associated with the degree of calcification. In cultured SMCs, inorganic phosphate (Pi) stimulation dose-dependently increased SAβ-gal-positive cells, and Pi-induced senescence was associated with downregulation of SIRT1 expression, leading to p21 activa...

Sirtuin 1 Retards Hyperphosphatemia-Induced Calcification of Vascular Smooth Muscle Cells

Cardiovascular disease (CVD) is the number one leading cause for human mortality. Besides genetics and environmental factors, in recent years, gut microbiota has emerged as a new factor influencing CVD. Although cause-effect relationships are not clearly established, the reported associations between alterations in gut microbiota and CVD are prominent. Therefore, we hypothesized that machine learning (ML) could be used for gut microbiome-based diagnostic screening of CVD. To test our hypothesis, fecal 16S ribosomal RNA sequencing data of 478 CVD and 473 non-CVD human subjects collected through the American Gut Project were analyzed using 5 supervised ML algorithms including random forest, support vector machine, decision tree, elastic net, and neural networks. Thirty-nine differential bacterial taxa were identified between the CVD and non-CVD groups. ML modeling using these taxonomic features achieved a testing area under the receiver operating characteristic curve (0.0, perfect antidiscrimination; 0.5, random guessing; 1.0, perfect discrimination) of ≈0.58 (random forest and neural networks). Next, the ML models were trained with the top 500 high-variance features of operational taxonomic units, instead of bacterial taxa, and an improved testing area under the receiver operating characteristic curves of ≈0.65 (random forest) was achieved. Further, by limiting the selection to only the top 25 highly contributing operational taxonomic unit features, the area under the receiver operating characteristic curves was further significantly enhanced to ≈0.70. Overall, our study is the first to identify dysbiosis of gut microbiota in CVD patients as a group and apply this knowledge to develop a gut microbiome-based ML approach for diagnostic screening of CVD.

Machine Learning Strategy for Gut Microbiome-Based Diagnostic Screening of Cardiovascular Disease.

Aortic arch calcification detectable on chest X-ray is a strong independent predictor of cardiovascular events beyond traditional risk factors

Thoracic aortic calcification (TAC) is associated with adverse cardiovascular outcomes, and for the cardiovascular imager, is predominantly encountered in 4 settings: 1) incidentally, for e...

Thoracic Aortic Calcification: Diagnostic, Prognostic, and Management Considerations

Background:Given the link between cholesterol and activation of inflammation via interleukin 1β (IL-1β), we tested the effects of IL-1β inhibition on atherosclerotic calcification in mice. Patients with familial hypercholesterolemia develop extensive aortic calcification and calcific aortic stenosis. Although statins delay this process, low-density lipoprotein (LDL) cholesterol lowering alone is not enough to avert it. Data suggest that vascular inflammation initiated by hypercholesterolemia is followed by unchecked mineralization at sites of atherosclerotic plaques. The LDL-receptor (LDLR)-deficient (Ldlr−/−) and LDLR-attenuated Pcsk9(Tg) mice are available animal models for pharmacological testing.Methods:A mouse monoclonal antibody (mAb) against IL-1β or placebo was administered subcutaneously in Ldlr−/− and Pcsk9(Tg) models fed a Western diet. Drug level, anthropometric, lipid, and glucose profiles were determined. Expressions of proprotein convertase subtilisin/kexin type 9 (PCSK9), serum amyloid A1,...

Reducing Vascular Calcification by Anti-IL-1β Monoclonal Antibody in a Mouse Model of Familial Hypercholesterolemia.

Sodium alginate (SALG) is a substance derived from brown seaweed that has been shown to reduce blood pressure (BP). However, its effects on renovascular hypertension caused by 2-kidney, 1-clip (2K1C) are not yet clear. Previous research suggests that hypertensive rats have increased intestinal permeability, and that SALG improves the gut barrier in inflammatory bowel disease mouse models. Therefore, the goal of this study was to determine whether the antihypertensive effects of SALG involve the intestinal barrier in 2K1C rats. Rats were fed either a 1.0% SALG diet or a control diet for six weeks after being subjected to 2K1C surgery or a sham operation. The systolic BP was measured weekly, and the mean arterial BP was measured at the end of the study. Intestinal samples were taken for analysis, and plasma lipopolysaccharide (LPS) levels were measured. The results showed that BP in 2K1C rats was significantly higher than in SHAM rats when fed CTL, but not when fed SALG. The gut barrier in 2K1C rats was improved by SALG intake. Plasma LPS levels also differed depending on the animal model and diet. In conclusion, dietary SALG may alleviate 2K1C renovascular hypertension by altering the gut barrier.

/pdf/influence-of-intestinal-barrier-on-alleviating-an-increase-1qo5ypaa.pdf

Influence of Intestinal Barrier on Alleviating an Increase in Blood Pressure by Sodium Alginate Intake in 2-Kidney, 1-Clip Renovascular Hypertensive Rats

This study sought to investigate whether eating conditions affected the consumption and deliciousness of food. A total of 16 healthy university students were recruited and ate two types of meals (each with 770 kcal) similar to that provided in school lunches under two conditions (e.g., talking vs. silence while eating with group members) in a cross-over design. The amount of food left by the participants and the time needed to finish eating were measured. After eating, participants evaluated the deliciousness and enjoyment of each meal using a visual analog scale. Notably, no significant differences in the eating rate and palatability were observed between the four conditions. However, significant differences in enjoyment and feeding time were observed. These findings highlights the importance of ensuring that sufficient time with other people is spent when eating to realize the benefits of eating in a group.

Conversing with Others While Eating a School Lunch Affects Eating Enjoyment and Extends the Meal Time

Background: Arterial calcification is associated with cardiovascular (CV) disease, to be leading to vessel wall stiffness and causing the management of hemodynamics in the elderly more difficult. Here, we compared the extent of calcification in the aortic arch by reviewing chest X-rays to that in the abdominal aorta as assessed by more detailed examinations. In addition, the validity of the grading and the relationship of this useful grading to clinical risk factors were evaluated.Methods and Results: The extent of aortic arch calcification (AAC) on a postero-anterior plain chest X-ray was divided into four grades (0 to 3). First, AAC grade was assessed in patients who underwent two quantitative examinations for abdominal aortic calcification; lateral radiograph of lumbar spine and/or computer tomography, and was positively correlated with the abdominal aortic calcification level. Subsequently, AAC grade in 239 out-patients (115 men; mean age, 61.9 years) was also evaluated, and was 0, 1, 2, and 3 in 46%, 22%, 29%, and 4% of the population, respectively, was significantly associated with pulse pressure and intima-media thickness. AAC grade in patients with diabetes or renal dysfunction was significantly higher than in those without each risk, but there was no association with other risk factors. In addition, AAC grade was positively correlated with risk factor clustering.Conclusion: Assessment of AAC detectable on a chest X-ray is very useful and its grade reflects the magnitude of calcified change in the whole aorta. In addition, AAC evaluation may provide supportive information for atherosclerotic risk stratification.

/pdf/validity-and-usefulness-of-aortic-arch-calcification-in-1exrnpvjv9.pdf

Validity and Usefulness of Aortic Arch Calcification in Chest X-ray

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Aortic arch calcification detectable on chest X-ray is a strong independent predictor of cardiovascular events beyond traditional risk factors

Influence of Intestinal Barrier on Alleviating an Increase in Blood Pressure by Sodium Alginate Intake in 2-Kidney, 1-Clip Renovascular Hypertensive Rats

Conversing with Others While Eating a School Lunch Affects Eating Enjoyment and Extends the Meal Time

Validity and Usefulness of Aortic Arch Calcification in Chest X-ray